Induction of mossy fiber→CA3 long-term potentiation requires translocation of synaptically released Zn2+

被引:224
作者
Li, Y
Hough, CJ
Frederickson, CJ
Sarvey, JM
机构
[1] Uniformed Serv Univ Hlth Sci, Dept Pharmacol, Bethesda, MD 20814 USA
[2] Uniformed Serv Univ Hlth Sci, Dept Psychiat, Bethesda, MD 20814 USA
[3] Univ Texas, Med Branch, Dept Biomed Engn, Galveston, TX 77550 USA
[4] Univ Texas, Med Branch, Dept Anat, Galveston, TX 77550 USA
[5] Univ Texas, Med Branch, Dept Neurosci, Galveston, TX 77550 USA
[6] NeuroBio Tex Inc, Galveston, TX 77550 USA
关键词
zinc; long-term potentiation; CA3; hippocampus; CaEDTA; mossy fiber; plasticity; Na-pyrithione; Newport Green; synaptic transmission;
D O I
10.1523/JNEUROSCI.21-20-08015.2001
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The mammalian CNS contains an abundance of chelatable Zn2+ sequestered in the vesicles of glutamatergic terminals. These vesicles are particularly numerous in hippocampal mossy fiber synapses of the hilar and CA3 regions. Our recent observation of frequency-dependent Zn2+ release from mossy fiber synaptic terminals and subsequent entry into postsynaptic neurons has prompted us to investigate the role of synaptically released Zn2+ in the induction of long-term potentiation (LTP) in field CA3 of the hippocampus. The rapid removal of synaptically released Zn2+ with the membrane-impermeable Zn2+ chelator CaEDTA (10 mM) blocked induction of NMDA receptor-independent mossy fiber LTP by high-frequency electrical stimulation (HFS) in rat hippocampal slices. Mimicking Zn2+ release by bath application of Zn2+ (50-100 muM) without HFS induced a long-lasting potentiation of synaptic transmission that lasted more than 3 hr. Moreover, our experiments indicate the effects of Zn2+ were not attributable to its interaction with extracellular membrane proteins but required its entry into presynaptic or postsynaptic neurons. Co-released glutamate is also essential for induction of LTP under physiological conditions, in part because it allows Zn2+ entry into postsynaptic neurons. These results indicate that synaptically released Zn2+, acting as a second messenger, is necessary for the induction of LTP at mossy fiber-->CA3 synapses of hippocampus.
引用
收藏
页码:8015 / 8025
页数:11
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